Abstract

Organic polymers are materials widely used in our daily lives, such as daily necessities, foods, and medicines. There have been reports recently that cross-linked polyacrylic acid (CL-PAA) can possibly cause serious lung disease. We investigated whether intratracheal instillation of CL-PAA causes pulmonary disorder in rats. Male F344 rats were administered low (0.2mg/rat) and high (1.0mg/rat) doses of CL-PAA intratracheally and were dissected 3 days, 1week, 1month, 3months, and 6months after exposure to examine inflammatory and fibrotic responses in the lungs. Only the high-dose specimens were subjected to ultrasonic dispersion treatment of the administered material. There was a dose-dependent increase in the total cell count, neutrophil count, neutrophil percentage, lactate dehydrogenase (LDH), surfactant protein D (SP-D), cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2 values in bronchoalveolar lavage fluid (BALF) from 3 days to at least 3months after intratracheal administration of CL-PAA. Heme oxygenase-1 (HO-1) in lung tissue was also persistently elevated from 3 days to 6months after exposure. Alkaline phosphatase (ALP) in BALF was elevated at 3 days and 1month after exposure only in the high-dose group. Histopathological findings in lung tissue showed inflammatory and fibrotic changes from 3 days after administration, and we observed obvious inflammatory changes for up to 3months and fibrotic changes for up to 6months. Intratracheal administration of CL-PAA induced persistent neutrophilic inflammation and fibrosis in the rats' lungs, suggesting that CL-PAA may have inflammogenic and fibrogenic effects.

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